Parris C N, Jezzard S, Silver A, MacKie R, McGregor J M, Newbold R F
Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex, UK.
Br J Cancer. 1999 Jan;79(1):47-53. doi: 10.1038/sj.bjc.6690010.
Telomeres are specialized structures consisting of repeat arrays of TTAGGGn located at the ends of chromosomes. They are essential for chromosome stability and, in the majority of normal somatic cells, telomeres shorten with each cell division. Most immortalized cell lines and tumours reactivate telomerase to stabilize the shortening chromosomes. Telomerase activation is regarded as a central step in carcinogenesis and, here, we demonstrate telomerase activation in premalignant skin lesions and also in all forms of skin cancer. Telomerase activation in normal skin was a rare event, and among 16 samples of normal skin (one with a history of chronic sun exposure) 12.5% (2 out of 16) exhibited telomerase activity. One out of 16 (6.25%) benign proliferative lesions, including viral and seborrhoeic wart samples, had telomerase activity. In premalignant actinic keratoses and Bowen's disease, 42% (11 out of 26) of samples exhibited telomerase activity. In the basal cell carcinoma and cutaneous malignant melanoma (CMM) lesions, telomerase was activated in 77% (10 out of 13) and 69% (22 out of 32) respectively. However, only 25% (3 out of 12) of squamous cell carcinomas (SCC) had telomerase activity. With the exception of one SCC sample, telomerase activity in a positive control cell line derived from a fibrosarcoma (HT1080) was not inhibited when mixed with the telomerase-negative SCC or CMM extracts, indicating that, overall, Taq polymerase and telomerase inhibitors were not responsible for the negative results. Mean telomere hybridizing restriction fragment (TRF) analysis was performed in a number of telomerase-positive and -negative samples and, although a broad range of TRF sizes ranging from 3.6 to 17 kb was observed, a relationship between telomerase status and TRF size was not found.
端粒是位于染色体末端的由TTAGGGn重复序列组成的特殊结构。它们对于染色体稳定性至关重要，并且在大多数正常体细胞中，端粒会随着每次细胞分裂而缩短。大多数永生化细胞系和肿瘤会重新激活端粒酶以稳定缩短的染色体。端粒酶激活被视为致癌过程中的关键步骤，在此，我们证明了癌前皮肤病变以及所有类型的皮肤癌中均存在端粒酶激活现象。正常皮肤中端粒酶激活是罕见事件，在16份正常皮肤样本（其中1份有慢性阳光暴露史）中，12.5%（16份中的2份）表现出端粒酶活性。16份良性增殖性病变样本（包括病毒疣和脂溢性疣样本）中有1份（6.25%）具有端粒酶活性。在癌前光化性角化病和鲍温病中，42%（26份中的11份）样本表现出端粒酶活性。在基底细胞癌和皮肤恶性黑色素瘤（CMM）病变中，端粒酶激活率分别为77%（13份中的10份）和69%（32份中的22份）。然而，只有25%（12份中的3份）的鳞状细胞癌（SCC）具有端粒酶活性。除1份SCC样本外，源自纤维肉瘤的阳性对照细胞系（HT1080）的端粒酶活性在与端粒酶阴性的SCC或CMM提取物混合时未受到抑制，这表明总体而言，Taq聚合酶和端粒酶抑制剂并非导致阴性结果的原因。对一些端粒酶阳性和阴性样本进行了平均端粒杂交限制片段（TRF）分析，尽管观察到TRF大小范围从3.6至17 kb很广，但未发现端粒酶状态与TRF大小之间存在关联。
